Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency.

Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette-Guérin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by Herpesviridae viruses. Attenuated live measles, mumps, and rubella and/or varicella zoster virus vaccines triggered severe reactions in the five patients with complete deficiency who were vaccinated. Seven patients developed features of hemophagocytic syndrome. Twenty-one patients died, and death was almost twice as likely in patients with complete STAT1 deficiency than in those with partial STAT1 deficiency. All but one of the eight survivors with AR complete deficiency underwent hematopoietic stem cell transplantation. Overall survival after hematopoietic stem cell transplantation was 64%. A diagnosis of AR STAT1 deficiency should be considered in children with mycobacterial and/or viral infectious diseases. It is important to distinguish between complete and partial forms of AR STAT1 deficiency, as their clinical outcome and management differ significantly.

Mendelian Susceptibility to Mycobacterial Disease Caused by a Novel Founder IL12B Mutation in Saudi Arabia.

PURPOSE: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare primary immunodeficiency predisposing congenitally affected individuals to diseases caused by weakly virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccine strains and environmental mycobacteria. IL-12p40 deficiency is a genetic etiology of MSMD resulting in impaired IL-12- and IL-23-dependent IFN-γ immunity. Most of the reported patients with IL-12p40 deficiency originate from Saudi Arabia (30 of 52) and carry the recurrent IL12B mutation c.315insA (27 of 30). METHODS: Whole-exome sequencing was performed on three patients from two unrelated kindreds from Saudi Arabia with disseminated disease caused by a BCG vaccine substrain. RESULTS: Genetic analysis revealed a homozygous mutation, p.W60X, in exon 3 of the IL12B gene, resulting in complete IL12p40 deficiency. This mutation is recurrent due to a new founder effect. CONCLUSIONS: This report provides evidence for a second founder effect for recurrent mutations of IL12B in Saudi Arabia.

Diagnosis and management of community-acquired urinary tract infection in infants and children: Clinical guidelines endorsed by the Saudi Pediatric Infectious Diseases Society (SPIDS).

Urinary tract infection (UTI) is the most common bacterial disease in childhood worldwide and may have significant adverse consequences, particularly for young children. In this guideline, we provide the most up-to-date information for the diagnosis and management of community-acquired UTI in infants and children aged over 90 days up to 14 years. The current recommendations given by the American Academy of Pediatrics Practice guidelines, Canadian Pediatric Society guideline, and other international guidelines are considered as well as regional variations in susceptibility patterns and resources. This guideline covers the diagnosis, therapeutic options, and prophylaxis for the management of community-acquired UTI in children guided by our local antimicrobial resistance pattern of the most frequent urinary pathogens. Neonates, infants younger than three months, immunocompromised patients, children recurrent UTIs, or renal abnormalities should be managed individually because these patients may require more extensive investigation and more aggressive therapy and follow up, so it is considered out of the scope of these guidelines. Establishment of children-specific guidelines for the diagnosis and management of community-acquired UTI can reduce morbidity and mortality. We present a clinical statement from the Saudi Pediatric Infectious Diseases Society (SPIDS), which concerns the diagnosis and management of community-acquired UTI in children.

Safety and tolerability of moxifloxacin for the treatment of disseminated BCGitis in children.

BACKGROUND AND OBJECTIVE: Disseminated BCGitis is a rare but serious complication of BCG vaccine in patients with underlying primary immunodeficiency. Fluoroquinolone antibiotics containing antimycobacterial regimen have been considered in the treatment of disseminated BCGitis, but there are limited data about the dosing, safety, and tolerability of fluoroquinolone such as moxifloxacin in children. The aim of this study was to report the experience with the dosing, safety, and tolerability of moxifloxacin in children with disseminated BCGitis. METHOD: This retrospective descriptive study included children who had been diagnosed with disseminated BCGitis and treated with an antimycobacterial regimen including moxifloxacin for more than two weeks from 2007 to 2017 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. RESULT: Ten children were included: six (60.0%) were male and four (40.0%) were female. The primary diagnosis for five patients was Mendelian susceptibility to mycobacterial diseases (MSMD), four patients were diagnosed with severe combined immune deficiency (SCID), and the remaining patient had human immunodeficiency virus (HIV) infection. The overall mean duration of moxifloxacin treatment was 10.1 months. Liver toxicity was recorded in three patients. The most common medications used with moxifloxacin were ethambutol and clarithromycin. Moxifloxacin serum concentration level was determined in 5 patients. No musculoskeletal side effects were reported while the patient was on moxifloxacin. The treated patients showed a different response to an antimycobacterial regimen including moxifloxacin, with mortality in two patients. CONCLUSION: Our study suggests that moxifloxacin is generally tolerated in children and might be considered in disseminated BCGitis cases. Additionally, paying attention to side effects such as liver toxicity is recommended, particularly with the use of other antimycobacterial antibiotics, which could also be hepatotoxic. A moxifloxacin-containing regimen for disseminated BCGitis showed clinical improvement in some patients in this study, although the majority presented the same clinical condition.

Departmental collaborative approach for improving in-patient clinical documentation (five years experience).

INTRODUCTION: Health care institutes are cooperative areas where multiple health care services come together and work closely; physician, nurses and paramedics etc,. These multidisciplinary teams usually communicate with each other by documentation. Therefore, accurate documentation in health care organization is considered one of the vital processes. To make the documentation useful, it needs to be accurate, relevant, complete and confidential. OBJECTIVES: The aim of this paper is to demonstrate the effect of the collaborative work in the Department of Pediatrics on improving the quality of inpatient clinical documentation over 5 years. METHODS: Improving clinical documentations went through several collaborative approaches, these include: Departmental Administration involvement, establishment of quality management team, regular departmental collaborative meeting as a monitoring and motivating tool, establishment of the residents quality team, Integration of quality projects into the new residents annual orientation, considering it as a part of the trainee personal evaluation, sending reminders to the consultants and residents on the adherence for admission note initiating and 24 h's verification, utilization of standardized template of admission note and progress note and emphasizing on the adherence to the approved medical abbreviation list only for any abbreviation to be used. RESULTS: During the period between the first quarter of 2012 to the fourth quarter of 2017; a significant improvement was noticed in the overall in-patient clinical documentation compliance rate, as it was ranging from lower 50% in 2012 and 2013, and increased gradually to reach upper 80% in the last quarters of 2016 and 2017. These figures are based on an independent audit that being done by the hospital quality management department and received by the department in a quarterly basis. CONCLUSION: Despite multiple challenges for improving the compliance for clinical documentations, major improvement can be achieved when the collaboration and efforts among all stakeholders being shared and set as a common goal.

Challenges of implementing a standardized process for discharge summaries (5 years experience).

INTRODUCTION: Discharge summaries are essential documents to provide a long-lasting record of a patient's visit to a hospital. It provides an effective method of communication between various hospital services and primary care providers.We conducted a study recently in KFSH&RC recommending that every admitted patient to the Pediatric Department must have a discharge summary initiated as soon as possible within the first five days of hospitalization and to be updated periodically until its completion on the patient's discharge day. Results of this study showed that most of the patients received their discharge summaries within the time limit as recommended by the JCIA standard. OBJECTIVES: The aim of this paper is to present our department's experience in regard to the difficulties, challenges, and outcomes of the adopted work flow for discharge summaries over a period of five years. METHODS: The residents have been instructed to initiate the discharge summaries as soon as possible within the first five days of hospitalization for every patient admitted under the Department of Pediatrics regardless of the expected discharge date. Afterward, it will be the responsibility of the attending junior and senior residents to update the summaries on regular basis as long as the patient under their care. They should transfer the updated summary to the coming resident that will take over the medical care until the discharge day when the most recent update will be forwarded to the attending consultant for final review and signature. RESULTS: Between 2011 and 2016, a significant drop in the number of delinquent records was noted. From 1131 delinquent records at the end of the fourth quarter of 2011, the number has fallen to 15 in the fourth quarter of 2016. Furthermore, compliance to JCIA documentation standards showed sustained improvement since the initiation of the project. The department used to score around 50% in the discharge documentation compliance rate which has improved to be maintained around 80%s in average. CONCLUSIONS: Every new project concerning the quality of patient care provided in any institution is expected to face multiple challenges and difficulties. Proper identifications of the challenges, standardize approach for solutions, sustainability of quality monitoring for an improvement projects can maintain the success for any new project.

Bacillus Calmette-Guérin vaccine related lymphadenitis in children: Management guidelines endorsed by the Saudi Pediatric Infectious Diseases Society (SPIDS).

The Bacillus Calmette-Guérin (BCG) vaccine contains live attenuated Mycobacterium bovis; was first used in humans to prevent tuberculosis (TB) in 1921. The World Health Organization (WHO) established the Expanded Program on Immunization in 1974 to ensure that all children have access to routinely recommended vaccines including BCG. Each year 120 million doses of BCG vaccine are administered worldwide. Intradermal BCG vaccine gives rise to a classic primary complex that consists of a cutaneous nodule at the site of injection and subclinical involvement of the regional lymph nodes, which is self-limiting and requires no treatment. However, ipsilateral regional lymph node enlargement may follow BCG vaccine and is considered as the most common complication, some progress to suppuration. Rarely a disseminated BCG infection may develop in immunocompromised individuals resulting in a devastating outcome. Within the last decades, variable strategies have been applied in treating lymphadenitis related to BCG vaccine, ranging from observation, anti-mycobacterial therapy, aspiration, incision and drainage to lymph node surgical excision. We are presenting these guidelines that intended to optimize and standardize management of various types of BCG related lymph adenitis in children. They are based upon the best available evidence in literature beside our experience in this field.

HIV-Care Outcome in Saudi Arabia; a Longitudinal Cohort.

BACKGROUND: Clinical characteristics of HIV-1 infection in people inhabiting Western, Sub-Saharan African, and South-East Asian countries are well recognized. However, very little information is available with regard to HIV-1 infection and treatment outcome in MENA countries including the Gulf Cooperation Council (GCC) states. METHODS: Clinical, demographic and epidemiologic characteristics of 602 HIV-1 infected patients followed in the adult Infectious Diseases Clinic of King Faisal Specialist Hospital and Research Centre, in Riyadh, Kingdom of Saudi Arabia a tertiary referral center were longitudinally collected from 1989 to 2010. RESULTS: Of the 602 HIV-1 infected patients in this observation period, 70% were male. The major mode of HIV-1 transmission was heterosexual contact (55%). At diagnosis, opportunistic infections were found in 49% of patients, most commonly being pneumocysitis. AIDS associated neoplasia was also noted in 6% of patients. A hundred and forty-seven patients (24%) died from the cohort by the end of the observation period. The mortality rate peaked in 1992 at 90 deaths per 1000 person-year, whereas the mortality rate gradually decreased to <1% from 1993-2010. In 2010, 71% of the patients were receiving highly active retroviral therapy. CONCLUSIONS: These data describe the clinical characteristic of HIV-1-infected patients at a major tertiary referral hospital in KSA over a 20-year period. Initiation of antiretroviral therapy resulted in a significant reduction in both morbidity and mortality. Future studies are needed in the design and implementation of targeted treatment and prevention strategies for HIV-1 infection in KSA.